Search

Abstract Objectives To prove our hypothesis that acyclovir prophylaxis in autologous hematopoietic stem cell transplantation (AHSCT) recipients with hematologic malignancies (HM) reduces the incidence of chemotherapy-induced oral mucositis (CIOM) by inhibiting the intraoral HSV reactivation during the neutropenic period, we conducted a randomized phase II study of acyclovir for the prevention of CIOM in adult HSV sero-positive AHSCT recipients. Methods Patients were randomized to either the study group (acyclovir 400 mg PO bid until neutrophil engraftment) or the control group (no prophylaxis) and received AHSCT. Oral examination and sampling for HSV were performed at three timepoints of AHSCT. Results In 54 patients who were randomized (for intention-to-analysis), the incidence of CIOM was 16.0% (4/25 patients) and 58.6% (17/29 patients) in the study group and the control group, respectively (P = 0.001). In 49 patients who completed the study (for per-protocol analysis), the incidence of CIOM was 13.0% (3/23 patients) and 61.5% (16/26 patients) in the study group and the control group, respectively (P = 0.001). In addition, HSV-1 PCR positivity in the study group was significantly lower than that the control group (4.3% vs. 46.2%, P = 0.001). A strong association between the HSV-1 reactivation status and CIOM was reconfirmed. Conclusions Prophylactic use of oral acyclovir effectively reduced the incidence of CIOM in patients with HM who were undergoing AHSCT. Trial registrations This trial was registered at the Clinical Research Information Service in the Republic of Korea under the number KCT0003885 (registration date 03/05/2019).

Abstract Background Tachykinins and their cognate receptors, neurokinin receptors (NKs) including NK1, NK2, and NK3 play vital roles in regulating various physiological processes including neurotransmission, nociception, inflammation, smooth muscle contractility, and stimulation of endocrine and exocrine gland secretion. Their abnormal expression has been reported to be associated with neurological disorders, inflammation, and cancer. Even though NKs are expressed in the same cells with their expression being inversely correlated in some conditions, there is no direct evidence to prove their interaction. Understanding the functional crosstalk between NKs in mediated downstream signaling and cellular responses may elucidate the roles of each receptor in pathophysiology. Results In this study, we showed that NKs were co-expressed in some cells. However, different from NK3, which only forms homodimerization, we demonstrated a direct interaction between NK1 and NK2 at the protein level using co-immunoprecipitation and NanoBiT-based protein interaction analysis. Through heterodimerization, NK2 downregulated substance P-stimulated NK1 signals, such as intracellular Ca2+ mobilization and ERK phosphorylation, by enhancing β-arrestin recruitment, even at the ligand concentration that could not activate NK2 itself or in the presence of NK1 specific antagonist, aprepitant. In A549 cells with receptors deleted and reconstituted, NK2 exerted a negative effect on substance P/NK1-mediated cell migration. Conclusion Our study has provided the first direct evidence of an interaction between NK1 and NK2, which highlights the functional relevance of their heterodimerization in cellular responses. Our findings demonstrated that through dimerization, NK2 exerts negative effects on downstream signaling and cellular response mediated by NK1. Moreover, this study has significant implications for understanding the complexity of GPCR dimerization and its effect on downstream signaling and cellular responses. Given the important roles of tachykinins and NKs in pathophysiology, these insights may provide clues for developing NKs-targeting drugs.

Abstract To evaluate the associations of periodontal disease (PD) with systemic diseases, including diabetes mellitus (DM) and cardiovascular disease (CVD), as well as the reciprocal association. The CVD included the cases of coronary heart disease and heart failure. A prospective study was conducted from 2007 to 2019 using linked data from three databases in Korea. Three separate study groups were formed to individually determine the risks of PD (n = 10,533), DM (n = 14,523) and CVD (n = 14,315). All diseases were confirmed based on physicians’ diagnoses using medical records and self-reports. Cox proportional hazard regression was applied with 95% confidence intervals (CIs) to obtain hazard ratios (HRs). PD was significantly associated with an elevated risk of DM (HR [95% CI]: 1.22 [1.07–1.39]) after full adjustment for age, sex, lifestyle factors, body mass index, dental behaviour and CVD. PD was also found to increase the risk of CVD (1.27 [1.03–1.57]), whereas CVD increased the risk of PD (1.20 [1.09–1.32]) after full adjustment for other covariates including DM. This study found a bidirectional association between PD and CVD, as well as a positive association of PD with DM.

Abstract Background The oral health status of inmates in South Korean correctional institutions is poor, mainly due to limited resources and an unestablished triage system. Hence, this study aimed to develop a newly structured dental triage system for South Korean correctional institutions, using the British triage system as a reference. Methods This study included 32 public health dentists working at correctional institutions in South Korea in 2020, accounting for the entire population of public health dentists that year. Data on the dentists’ evaluation of resources and perceptions of dental service items were collected using a self-administered online survey including 19 dental service items from the British triage system to assess the level of agreement on dental triage items. All responses were recorded within 1 week of request, and a hierarchical cluster analysis was performed to develop a new dental triage system. Results The survey included 31 respondents working at 47 correctional institutions; 16, 14, and one respondent provided dental services at one, two, and three institutions, respectively. Among the correctional institutions, 2%, 74%, and 23% were the National Forensic Hospital, prisons, and detention centres, respectively. The hierarchical cluster analysis identified four adjusted dental triage categories: emergency, urgent, routine, and checkups, mainly in accordance with those in the British system, but a few items were reallocated. The new dental triage system was compared to the existing system and found to have higher specificity and sensitivity, indicating that it may be more effective at meeting the oral health needs of inmates in South Korean correctional institutions. Conclusions This study developed a newly structured dental triage system by adjusting the British system and evaluated its efficacy compared to the existing system. The new system may help improve the oral health status of inmates in South Korean correctional institutions by providing a more organized approach to dental care provision.

Abstract Background Dental care in cancer patients tends to be less prioritized. However, limited research has focused on major dental treatment events in cancer patients after the diagnosis. This study aimed to examine dental treatment delays in cancer patients compared to the general population using a national claims database in South Korea. Method The Korea National Health Insurance Service-National Sample Cohort version 2.0, collected from 2002 to 2015, was analyzed. Treatment events were considered for stomatitis, tooth loss, dental caries/pulp disease, and gingivitis/periodontal disease. For each considered event, time-dependent hazard ratios and associated 95% confidence intervals were calculated by applying a subdistribution hazard model with time-varying covariates. Mortality was treated as a competing event. Subgroup analyses were conducted by type of cancer. Results The time-dependent subdistribution hazard ratios (SHRs) of stomatitis treatment were greater than 1 in cancer patients in all time intervals, 2.04 within 30 days after cancer diagnosis, and gradually decreased to 1.15 after 5 years. The SHR for tooth loss was less than 0.70 within 3 months after cancer diagnosis and increased to 1 after 5 years. The trends in SHRs of treatment events for other dental diseases were similar to those observed for tooth loss. Subgroup analyses by cancer type suggested that probability of all dental treatment event occurrence was higher in head and neck cancer patients, particularly in the early phase after cancer diagnosis. Conclusion Apart from treatments that are associated with cancer therapy, dental treatments in cancer patients are generally delayed and cancer patients tend to refrain from dental treatments. Consideration should be given to seeking more active and effective means for oral health promotion in cancer patients.

Abstract Background Correctional institution inmates have reduced access to dental care; however, a quantitative assessment of their oral health condition has not yet been performed in South Korea. Therefore, this study aimed to assess dental caries and compare the prevalence of dental caries and associated factors between inmates and the general South Korean population. Methods The dental records of two detention centers in South Korea were retrospectively analyzed to assess the clinical oral health condition of inmates using the Decayed, Missing, and Filled Teeth (DMFT) index and self-reported questionnaire. These data were compared with similar data obtained from the Korea National Health and Nutrition Examination Survey (KNHANES) for the general South Korean population. Results In total, 642 inmates were analyzed and compared with 13,345 KNHANES participants in the KNHANES. The inmate and KNHANES groups demonstrated significant intergroup differences, with a higher prevalence of untreated caries, DMFT, decayed teeth (DT), and missing teeth (MT) values among the inmates. The prevalence of untreated caries decreased according to the history of dental pain in the inmate group but increased in the KNHANES group. The decrease in DMFT with a history of dental pain was significant only in the inmate group. Furthermore, self-rated oral health was significantly associated with prevalence of untreated caries, DMFT, DT, MT, and filled teeth (FT) in the inmate group but with prevalence of untreated caries, DMFT, DT, and MT in the KNHANES group. It was found that this is because there is an interaction effect by the group. Conclusions The oral health of the inmate group was significantly poorer than that of the general group. Since DMFT, DT, MT, and FT values and prevalence of untreated caries in the inmate group were significantly related to their self-rated oral health, suggesting that self-rated oral health should be incorporated into the dental health screenings of correctional institution inmates.

Wearing a face mask was strongly recommended during the COVID-19 pandemic. The purpose of this study was to investigate the diversity of the oral microbiome, the abundance of each bacterium on the inner surface of the mask, and the effects of xerostomia on the microbiota. The study was conducted on 55 generally healthy adults (45 women and 10 men, mean age 38.18 ± 12.49 years). Unstimulated flow rate (UFR) and stimulated flow rate (SFR) were measured in whole saliva samples collected for each condition. The 14 major oral bacterial species, including Porphyromonas gingivalis (P. gingivalis), Lactobacillus casei (L. casei), Tannerella forsythia (T. forsythia), and Treponema denticola (T. denticola) on the inner surface of the mask and in the UFR and SFR samples, were analyzed by real-time PCR. We found that the total DNA copy number of oral bacteria was significantly higher in UFR and SFR than in the mask (p 0.05). In summary, oral bacteria migrated to and existed on the inside of the mask, and the presence of xerostomia did not affect the bacterial profiles. The inner surface of the mask had an independent oral microbiome profile, although this showed lower quantity and diversity than the UFR and SFR samples.

Summary: Salivary gland cells, which secrete water in response to neuronal stimulation, are closely connected to other neurons. Transcriptomic studies show that salivary glands also express some proteins responsible for neuronal function. However, the physiological functions of these common neuro-exocrine factors in salivary glands are largely unknown. Here, we studied the function of Neuronal growth regulator 1 (NEGR1) in the salivary gland cells. NEGR1 was also expressed in mouse and human salivary glands. The structure of salivary glands of Negr1 knockout (KO) mice was normal. Negr1 KO mice showed tempered carbachol- or thapsigargin-induced intracellular Ca2+ increases and store-operated Ca2+ entry. Of interest, the activity of the large-conductance Ca2+-activated K+ channel (BK channel) was increased, whereas Ca2+-activated Cl− channel ANO1 channel activity was not altered in Negr1 KO mice. Pilocarpine- and carbachol-induced salivation was decreased in Negr1 KO mice. These results suggest that NEGR1 influence salivary secretion though the muscarinic Ca2+ signaling.

Abstract Background C–C motif chemokine receptor 2 (CCR2), the main receptor for monocyte chemoattractant protein-1 (MCP-1), is expressed on immune cells, including monocytes, macrophages, and activated T cells, and mediates cell migration toward MCP-1 in inflammation-related diseases. The CCR2 gene encodes two isoforms: CCR2A and CCR2B. The CCR2B open reading frame is localized in a single exon, similar to other chemokine receptors, and CCR2A and CCR2B feature different amino acid sequences in their C-terminal intracellular loops due to alternative splicing. Most biochemical studies on CCR2-related cellular responses in the immune system have focused on CCR2B, with few reports focused on CCR2A. Understanding the functional properties of CCR2A in cellular responses may elucidate the roles played by MCP-1 and CCR2 in pathophysiological responses. Results CCR2 gene expression analysis in several cell types revealed that most adherent cells only expressed CCR2A, whereas CCR2B expression was dominant in monocytic cells. The C-terminal Helix 8 region of CCR2A contains few basic amino acids, which may be unfavorable for cell surface localization, as confirmed with the HiBiT assay. CCR2B contains many C-terminal Ser/Thr residues, similar to other chemokine receptors, which may be phosphorylated by G protein–coupled receptor kinases (GRKs) to promote β-arrestin recruitment and subsequent endocytosis. By contrast, CCR2A contains few C-terminal Ser/Thr residues, which are unlikely to be phosphorylated by GRKs. CCR2A localized on the cell surface is resistant to internalization, despite the interaction between Gβ and GRKs induced by ligand binding with CCR2A. CCR2A induced cellular responses at a relatively higher degree than CCR2B, although both receptors mediated signaling events through Gαq and Gαi. HeLa cells lacking CCR2A showed slowed growth compared with parent cells, regardless of MCP-1 stimulation, and their chemotactic activity toward MCP-1, in addition to basal motility, was significantly impaired. Conclusion MCP-1 and CCR2 may play pivotal roles in cancer progression by recruiting macrophages into cancer tissue. This study demonstrates that CCR2A but not CCR2B is expressed in solid cancer–derived cells. CCR2A is resistant to internalization by β-arrestin due to a distinct C-terminal region from CCR2B, which enhances MCP-1-stimulated responses, indicating that CCR2A may play essential roles in solid cancer progression.

When diagnosing orofacial pain, clinicians should also consider non-odontogenic origin and systemic diseases as possible etiological factors, along with odontogenic origin. This case report aimed to provide information for early detection of orofacial pain of cardiac origin by dentists, when pain due to coronary artery disease is the only presenting symptom. A 60-year-old male patient with unexplained isolated bilateral jaw pain that had persisted for the past 5 years was referred to a dentist by an anesthesiologist who suspected temporomandibular joint disorder. In oral examination, no specific pathological changes were observed in the oral cavity, including teeth, surrounding alveolar bone, and buccal mucosa. Magnetic resonance imaging and conventional radiography showed no pathological destruction or abnormalities of bone and soft tissue in the temporomandibular joint region. However, pain was precipitated by ordinary daily activities, and the pain alleviating factor was rest. Eventually, the patient was referred to a cardiologist for further evaluation since his pain was induced by physical activity. Coronary artery disease (CAD) was diagnosed using coronary computed tomography angiography, and the pain was considered to be angina pectoris. Percutaneous coronary intervention was successfully done for the patient, after which his orofacial symptoms disappeared. To conclude, isolated craniofacial pain of cardiac origin may lead to patients seeking dental care or visiting orofacial pain clinics. In these settings, dentists and orofacial pain specialists may contribute to the diagnosis of CAD and refer patients for cardiac evaluation and appropriate management.

C-X-C motif chemokine ligand 12(CXCL12) is an essential chemokine for organ development and homeostasis in multiple tissues. Its receptor, C-X-C chemokine receptor type 4(CXCR4), is expressed on the surface of target cells. The chemokine and receptor are expressed almost ubiquitously in human tissues and cells throughout life, and abnormal expression of CXCL12 and CXCR4 is observed in pathological conditions, such as inflammation and cancer. CXCR4 is reportedly translated into five splicing variants of different lengths, which each have different amino acids in the N-terminus. As the N-terminus is the first recognition site for chemokines, CXCR4 variants may respond differently to CXCL12. Despite these differences, the molecular and functional properties of CXCR4 variants have not been thoroughly described or compared. Here, we explored the expression of CXCR4 variants in cell lines and analyzed their roles in cellular responses using biochemical approaches. RT-PCR revealed that most cell lines express more than one CXCR4 variant. When expressed in HEK293 cells, the CXCR4 variants differed in protein expression efficiency and cell surface localization. Although variant 2 demonstrated the strongest expression and cell surface localization, variants 1, 3, and 5 also mediated chemokine signaling and induced cellular responses. Our results demonstrate that the N-terminal sequences of each CXCR4 variant determine the expression of the receptor and affect ligand recognition. Functional analyses revealed that CXCR4 variants may also affect each other or interact during CXCL12-stimulated cellular responses. Altogether, our results suggest that CXCR4 variants may have distinct functional roles that warrant additional investigation and could contribute to future development of novel drug interventions.

Abstract Orthopantomogram (OPG) is important for primary diagnosis of temporomandibular joint osteoarthritis (TMJOA), because of cost and the radiation associated with computed tomograms (CT). The aims of this study were to develop an artificial intelligence (AI) model and compare its TMJOA diagnostic performance from OPGs with that of an oromaxillofacial radiology (OMFR) expert. An AI model was developed using Karas’ ResNet model and trained to classify images into three categories: normal, indeterminate OA, and OA. This study included 1189 OPG images confirmed by cone-beam CT and evaluated the results by model (accuracy, precision, recall, and F1 score) and diagnostic performance (accuracy, sensitivity, and specificity). The model performance was unsatisfying when AI was developed with 3 categories. After the indeterminate OA images were reclassified as normal, OA, or omission, the AI diagnosed TMJOA in a similar manner to an expert and was in most accord with CBCT when the indeterminate OA category was omitted (accuracy: 0.78, sensitivity: 0.73, and specificity: 0.82). Our deep learning model showed a sensitivity equivalent to that of an expert, with a better balance between sensitivity and specificity, which implies that AI can play an important role in primary diagnosis of TMJOA from OPGs in most general practice clinics where OMFR experts or CT are not available.

Background/Aims A link between oral cavity infections and chemotherapy-induced oral mucositis (CIOM) in patients with hematological malignancies (HMs) undergoing intensive chemotherapy (IC) or hematopoietic stem cell transplantation (HSCT) has been suggested. However, conclusive data are lacking, and there are no current guidelines for the prophylactic use of antimicrobials to prevent CIOM in these populations. Methods The relationships between herpes simplex virus (HSV) reactivation and Candida colonization in the oral cavity and CIOM in patients with HMs undergoing IC or HSCT were evaluated. Patients aged ≥ 19 years with HMs undergoing IC or HSCT were enrolled. Each patient was evaluated for HSV and Candida in the oral cavity along with CIOM at baseline and during the 2nd, 3rd, and 4th weeks. Results Seventy presentations among 56 patients were analyzed. CIOM was observed in 23 presentations (32.9%), with a higher incidence associated with HSCT (17 of 35 presentations, 48.6%) than with IC (six of 35 presentations, 8.6%). The reactivation of HSV-1 was significantly associated with an increased incidence of CIOM after adjusting for age, sex, type of disease, and treatment stage. A higher HSV-1 viral load was associated with an increased incidence of CIOM. The presence of Candida was not associated with CIOM. Conclusions HSV-1 reactivation in the oral cavity was highly associated with CIOM in patients with HMs undergoing high-dose chemotherapy.

Abstract Objective The objective of this study was to prospectively evaluate the clinical features of chemotherapy‐induced oral mucositis (CIOM) in adult patients with acute leukemia and the aggravating factors for such symptoms. Subjects Thirty‐seven prospective patients aged ≥19 years with acute leukemia undergoing chemotherapy were enrolled. Oral and clinical investigations were performed at baseline and on Day 14 after starting chemotherapy. The presence and severity of cancer‐induced oral mucositis were demonstrated using the World Health Organization (WHO) scoring system. Results On Day 14, we found that oral mucositis had developed in eight patients (21.6%). Hematopoietic stem cell transplantation (HSCT) in patients was a predictor of increased WHO scores (β = 1.937, p < .001). Regarding oral sites, ventral tongue (β = 1.670), soft palate (β = 1.242), and buccal mucosa (β = 0.593) were predictors for increased scores. In addition, the increase in WHO scores was positively correlated with the number of oral lesions (r = .521), the difficulty in eating (r = .250), and the overall oral health (r = .534; all p < .05). Conclusion The main factors affecting the severity of CIOM symptoms were the treatment with HSCT and the location of oral lesions. The incidence of CIOM and WHO scores were not significantly different between the subgroups of disease. Our findings will help clinicians investigate the oral findings after chemotherapy in adult patients with acute leukemia.

Activity-dependent fluid secretion is the most important physiological function of salivary glands and is regulated via muscarinic receptor signaling. Lipid rafts are important for G-protein coupled receptor (GPCR) signaling and ion channels in plasma membranes. However, it is not well understood whether lipid raft disruption affects all membrane events or only specific functions in muscarinic receptor-mediated water secretion in salivary gland cells. We investigated the effects of lipid raft disruption on the major membrane events of muscarinic transcellular water movement in human salivary gland (HSG) cells. We found that incubation with methyl-β-cyclodextrin (MβCD), which depletes lipid rafts, inhibited muscarinic receptor-mediated Ca2+ signaling in HSG cells and isolated mouse submandibular acinar cells. However, MβCD did not inhibit a Ca2+ increase induced by thapsigargin, which activates store-operated Ca2+ entry (SOCE). Interestingly, MβCD increased the activity of the large-conductance Ca2+-activated K+ channel (BK channel). Finally, we found that MβCD did not directly affect the translocation of aquaporin-5 (AQP5) into the plasma membrane. Our results suggest that lipid rafts maintain muscarinic Ca2+ signaling at the receptor level without directly affecting the activation of SOCE induced by intracellular Ca2+ pool depletion or the translocation of AQP5 into the plasma membrane.

Exosomes are nanosized vesicles (30−140 nm) of endocytic origin that play important roles in regenerative medicine. They are derived from cell membranes during endocytic internalization and stabilize in biological fluids such as blood and synovia. Temporomandibular joint osteoarthritis (TMJ OA) is a degenerative disease, which, in addition to chronic pain, is characterized by progressive cartilage breakdown, condylar bone remodeling, and synovitis. However, traditional clinical treatments have limited symptom- and structure-modifying effects to restore damaged cartilage and other TMJ tissues. This is due to the limited self-healing capacity of condylar cartilage. Recently, stem-cell-derived exosomes have been studied as an alternative therapeutic approach to tissue repair and regeneration. It is known that trophic regulation of mesenchymal stem cells (MSCs) has anti-inflammatory and immunomodulatory effects under pathological conditions, and research on MSC-derived exosomes is rapidly accumulating. MSC-derived exosomes mimic the major therapeutic effects of MSCs. They affect the activity of immune effector cells and possess multilineage differentiation potential, including chondrogenic and osteogenic differentiation. Furthermore, exosomes are capable of regenerating cartilage or osseous compartments and restoring injured tissues and can treat dysfunction and pain caused by TMJ OA. In this review, we looked at the uniqueness of TMJ, the pathogenesis of TMJ OA, and the potential role of MSC-derived exosomes for TMJ cartilage and bone regeneration.

Background: The SoUth Korean study to PrEvent cognitive impaiRment and protect BRAIN health through lifestyle intervention in at-risk elderly people (SUPERBRAIN) is a part of the World-Wide Finnish Geriatric Intervention Study to Prevent Cognitive Impairment and Disability (WW-FINGERS) network. This study aimed to demonstrate the effects of the SUPERBRAIN-based multidomain intervention with nutritional supplements in amyloid positive emission tomography (PET) proven early symptomatic Alzheimer's disease patients. Methods: Forty-six participants who were diagnosed with mild cognitive impairment or mild dementia and were positive in the amyloid PET study randomized into three groups: group A, the multidomain intervention with nutritional supplements; group B, nutritional supplements only; and a control group. The primary outcome was a change in the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) total scale index score after an 8-week intervention. Secondary outcomes, including gut microbiome data, were also analyzed. Results: The RBANS total scale index score improved significantly in group A compared with group B (p < 0.032) and compared with the control group (p < 0.001). After intervention, beta diversity of the gut microbiome between group A and the control group increased, and patients in group A were more enriched with Bifidobacterium. Conclusion: SUPERBRAIN-based multidomain intervention with nutritional supplements improves cognition and gut microbiota in patients with early symptomatic Alzheimer's disease who were amyloid-positive by PET. [ABSTRACT FROM AUTHOR]

In the South Korean study to prevent cognitive impairment and protect BRAIN health through lifestyle intervention in at-risk elderly people (SUPERBRAIN), we evaluated the impact of a 24-week facility-based multidomain intervention (FMI) and homebased MI (HMI) on white matter integrity. Among 152 participants, aged 60–79  years without dementia but with ≥1 modifiable dementia risk factor, 19 FMI, 20 HMI, and 16 controls underwent brain MRI at baseline and 24  weeks. Between the intervention and control groups, we compared changes in fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (AD) and radial diffusivity (RD) at regions-of-interest (ROI) including the cingulum cingulate gyrus (CgC), cingulum hippocampus (CgH), superior longitudinal fasciculus (SLF), as well as the uncinate fasciculus (UF). In addition, correlations between total and standard scores cognitive domains of the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) or serum brain-derived neurotrophic factor (BDNF) and changes in brain image measures were evaluated at a statistical significance level of p  <  0.05 (uncorrected for multiple corrections). The FA, MD, AD, and RD at each ROI at the baseline were not different among groups after Bonferroni correction. In the statistical analysis using two-way repeated measures ANOVA, any significant difference in longitudinal changes in the FA, MD, AD, and RD was not revealed. The statistical analysis, among the significant regions in paired t-test of the intervention group, compared with the control group, the FMI, HMI, and intervention group yielded significantly more beneficial effects on the AD of the CgC. In addition, longitudinal AD changes of the left CgC correlated with the BDNF changes (r  =  0.280, p  =  0.048). In this study, enhanced cognitive reserve after the multidomain lifestyle intervention could be revealed by changes in brain imaging for white matter integrity [ABSTRACT FROM AUTHOR]